Neuropsychology and Psychiatry With Dr. Jordan Grafman (NINDS), we have studied memory function in CFS. In addition, we are investigating the acute affects of a brief febrile episode in CFS patients and controls to determine whether CFS patients possess decreased neuropsychological reserve and prolonged reductions in performance following a brief illness. This is being done in the context of the interleukin-6 provocation study described below. With Drs. Garcia-Borregueros (NICHD) and Norman Rosenthal (NIMH) we published a controlled study of the rates of seasonality of symptoms on CFS. We found reduced seasonality that distinguishes CFS from seasonal affective disorder. Neuroendocrine Studies Since 1991, we have been studying aspects of hypothalamic-pituitary-adrenal axis regulation in CFS. In collaboration with Dr. Dimitri Papanicoleau and Dr. George Chrousos (NICHD), we are conducting a controlled study of responses to interleukin-6. CFS patients, healthy controls, patients with Fibromyalgia, and patients with depression are given a single dose of interleukin-6 which elicits a vigorous brief inflammatory response associated with headache, malaise, muscle aches, and fever, all which pass in six to eight hours. Interleukin-6 is an extremely potent stimulant of corticotropin releasing hormone from the hypothalamas. The response of this hormone and subsequent release of ACTH and cortisol will teach us more about the status of the HPA axis in CFS and other disorders. We are using the occasion of this brief induced illness to study the exacerbation of neurocognitive complaints if patients with CFS and in healthy controls (see above). Treatment We are now completing a placebo-controlled trial of fludricortisone for treatment of CFS. This study is being conducted as a distinct research project (ZOI-AI-00812-01- LCI). Eligibility for this study requires evidence of neurally- mediated hypotension in tilt table testing conducted at Johns Hopkins University by our collaborators, Drs. Peter Rowe and Hugh Calkins.